CDP-choline was discovered in 1955. In the case of most if not all of these supplements, the upregulation that occurs seems to “stick” so long as you keep taking them ie your new baseline DA levels will stay higher than your previous baseline levels. In rats, striatal DA levels were measured after 6 weeks of supplementation. I still can't really focus, but now feel a very light body sensation, and feel as if I can finally feel happiness. I haven't looked into the evidence behind/for the long half-life, but just from personal objective experience I've noticed what I presume are the effects of too much choline. In 2012 or 2013, things went in the tank for me…it’s like someone turned a light switch off. The meditation, excersise and b8 didnt give any actual data for the increase which leads me to believe receptor density increase by these methods are negligible. https://www.medschat.com/Drugs/half-life-calculator.asp. Furthermore, this does not appear to be related at all to Vitamin D levels. The elimination half-life is 56 hours for CO2 and 71 hours for urinary excretion. Pick one? I’m much calmer now then I used to be, I accept it and try to tell myself, maybe in a couple of hours. Been like 5 years on and off but mostly on . In this study, guinea pigs were given oral inositol (1.2 g/kg) for 12 weeks (about 15-20g a day for humans). I already take a stack with Alcar, NALT, and P.S. I'd get your choline from eggs as part of a meal, that way it is more gradually absorbed. It is as if a cloud has been lifted from my eyes and head. Any advice would be much appreciated. There are over 100 trillion synapses in the brain, and each one is used to send and receive chemical signals from neurons. Hence, CDP-choline is traditionally grouped with cholinergic rather than dopaminergic supplements. This means that sunlight is not only essential for synthesizing vitamin D in the body, but also for dopaminergic regulation. Looks like that second peak of choline was used to determine the 60hr hl of the parent compound cdp-choline. Required fields are marked *. It’s just scary when that happens. That 60 hour half life given to cdp choline may not be correct btw. Are there any drawbacks/side effects? Am i better off taking 250mg every 2 or 3 days? And last, I would cite the use of ultra low dose antipsychotic. CDP-Choline: Cytidine 5;-diphosphocholine, CDP-choline or citicoline is essential to the biosynthesis of phospholipids, like phosphatidylcholine. Citicoline is one of the most effective and well-researched nootropics available, and is a capable nootropic drug on its own right. In rats, CDP-choline raised noradrenaline, dopamine, and serotonin levels in the brain centers for memory, emotions, and movement [59, 60]. Various studies have found it to promote enhanced brain activity by supporting dopamine receptors and the synthesis of acetylcholine. Additionally, it is wise to educate yourself about exactly what these components actually do. This process is commonly referred to as reuptake inhibition. You can try using a half-life calculator to find a dosage. This is especially true with animal-sourced Vitamin A (i.e retinyl palmitate or palmitic acid, or cod liver oil because it is only one step away from being operational vitamin a as opposed to beta-carotene which is several. thank you for the informative and well-researched article. Once released, they are absorbed by the post-synaptic neurons as seen at the bottom. This applies to a lot of supplements actually, Vitamin A is another one that really isn't good to take in pure powder form because it spikes blood levels too fast and fucks with internal production. I think what I'll probably do if I ever decide to try another trial is dose on Monday, Wednesday, Saturday, or something like that, and see how I feel in 2 or 3 weeks. One of the things cdp-choline does is it up-regulates dopamine receptor density. I do think in some sense that you can consider these effects permanent even if it requires continued supplemention. Lately, the mental health benefits of exercise are gaining a lot of traction. That's a long time. Inositol, also referred to as Vitamin B8, is a molecule that is structurally similar to glucose. Does anyone know the reason behind this? In reality, these neurological processes are much more complex than this, but this will give you a general idea of how homeostasis works. So they both serve the same general purpose: a choline source so the body can make more acetylcholine but are metabolized differently, because they both shortcut to different parts of the acetylcholine production cycle. There is no universally accepted dosing regiment for uridine, it varies with the individual. I just started taking it today (added to my stack) but it won't be daily. That said I do think some of the supplements may induce lasting changing even upon cessation, uridine for instance actually repairs dopaminergic neurons and that in and of itself is a long-lasting effect. Both pre-synaptic and post-synaptic neurons contain receptors that regulate how much a neurotransmitter is released and how much it is absorbed. CDP-Choline, also called citicoline, is a naturally-occuring compound and nootropic that is typically supplemented to improve cognitive performance. This list will include both supplements and physical tasks; I will attempt to explain the mechanisms behind each in relationship to this goal. Would you advise using all these strategies together (obviously uridine and choline; yes)? For example, many people debate between taking CDP Choline (Citicoline) and Uridine, but you should base your decision on the type of stack that you are building and exactly what you want to achieve. There was a lot of talk last week about the results of the Parkinson’s Disease trial in the UK involving a surgery that implanted tubes in patients’ heads that could be used post-surgery to deliver GDNF and would hopefully regenerate dying dopamine brain cells. In order to get the same bang for your buck, you have to push the stakes higher, effectively pulling from an ever shrinking store of dopamine. Studies have found that it protects the brain from damage, boosts the levels of numerous neurotransmitters, and improves memory and learning. I just happened to see a post talking about the dosing of choline, regarding that too much can lead to a depressing effect. After seven months, levels of striatal DA were measured. The lone study stating this figure noticed bi-phasic spikes in plasma choline (not cdp-choline) post intake: the much larger of the two at two hours, the smaller, plateued peak at 24 hours. Lower levels of dopamine are released in response to stimuli (PMO) over time due to the Coolidge Effect. These self-correcting steady-state mechanisms of the brain are not limited to drugs of abuse; the brain is constantly making adjustments to maintain a consistent state, from even the most trivial of activities. I would start with uridine and/or cdp-choline to see how you react to them. After that I would incorporate inositol and eventually forskolin. If you want to skip ahead you can feel free to do so, but this information is worth knowing. CDP-Choline is unique as a choline source. I would like to give some food for thought: uridine and citicoline are probably redundant, because supplementation of one increase the other; the oral dosage for citicoline for a person of 75kg would be of about 1000mg, but as I know, sublingual administration increase bioavailability by a factor of 4-5, so the sublingual dosage shoud be 200-250mg to achieve 11% increase in D2 receptors (I don’t think that it is worth trying to achieve the 18% increase, because to less than double the dosage you have to increase dosage by a factor of five); even if percentage of receptors increase with inositol is not reported, I don’t think is negligible, because at high dosage it has the same efficacy of SSRIs for OCD and there are studies that reports a noticeable increase in SSRIs for OCD; about forskoline I don’t have a reference on dosage, but it worried me more than others supplements due to the risk of developing mania (inositol don’t increase responsiveness to amphetamine like substance, while forskoline does). This is because DA receptor densities decrease with age, at a rate of about 3% per decade.6https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1991.tb12471.x. Hi all, several years ago I collected a lot of research and notes about neurotransmitters and it’s modulators. Antidepressants like Zoloft and Prozac share this mechanism, but act as serotonin reuptake inhibitors instead. Additionally, given that rat lifespans are quite short, 7 months is quite a long time, which suggests these changes may be permanent. First off thank you for this wonderful article. I just started Nootropic stacking a few weeks ago, I am taking ALCAR, NALT, Citicoline, Lions Mane, Bacopa. It is made up of choline and cytidine. PC is rate-limited so that it just provides the building block for your body to take what it needs to make the right amount ACh without over-loading your brain with a direct precursor like CDP. Your email address will not be published. Have you noticed any of the classic pro-choline effects from phosphatidylcholine, verbal fluency, memory benefits, etc.? I would strongly suggest starting with uridine and/or cdp choline at smaller doses and work your way from there. If you’d rather not read the history, skip down to the bottom for my questions. 51,52 Several studies have investigated using CDP-choline as a supplement to levodopa. The only problem is that it will be harder to figure out the optimal doses for everything if you’re taking it all at once. There is now an increasingly large amount of evidence that exercise can increases DA receptor availability in the striatum.11https://www.ncbi.nlm.nih.gov/pubmed/26503310, In one study, exercise was shown to reduce the neurological damage that occurs from methamphetamine abuse. I eat (and cook) healthy, sleep enough, take long walks every day (not running, but not walking either:). Additionally, in my macroeconomics class I constantly surprised myself with how verbally fluent and confident I was when discussing the material with my professor in class. The brain contains about 100 billion neurons, and neurons are connected to one another in a complex web of synapses. Of those, the only one with notable side effects is forskolin, so I might suggest being more cautious with that. Do you mind if I ask some questions about your historical usage: 3-Have you seen tolerance effects (need more to get the same effect). Choline is the precursor to the neurotransmitter acetylcholine and can be obtained from foods in the form of phosphatidylcholine. My theory, and perhaps I should have explained this better, is that these changes last indefinitely as long as you keep taking the supplement(s). The study found that striatal D2/D3 receptor availability was significantly greater in the group with high exposure than the low exposure group. The result were promising: chronic inositol induced a significant increase in striatal D2 receptor density.8https://www.ncbi.nlm.nih.gov/pubmed/11267629 There was no data on whether this effect is maintained after treatment nor the degree to which the densities were changed depending on dosages used. You might start out feeling great and then hit depression and have to wait for it to clear your system. You say long term but there haven’t really been any long term studies on humans with these compounds right? Afterwards, it showed the same results as the previous study; increases in both the post and pre synaptic densities. It’s unclear which form of exercise is most effective. While this is a possibility, I find it very unlikely that this accounts for every individual case. Here’s another behavioral change you can implement to increase DA sensitivity. While scientific evidence on meditation is still in its infancy, there is emerging evidence of many incredible benefits to brain health and function. As a bountiful source of choline, citicoline aids in the transportation of dopamine, augmenting its release into the brain. Fortunately, there do appear some effective ways of increasing average DA levels over the long-term. Otherwise, the worry spirals out of control, turns into anxiety. Drugs like cocaine work preventing this “vacuuming” effect (typically by blocking the action of a transporter called DAT). Taken together, it would appear that uridine may upregulate DA by both preventing excessive DA levels and by repairing/restoring neuronal DA functionality. The goal of this study was to determine the effects of long-term meditation on eyeblink activity; the results of which can be used to infer the effects on striatal DA levels. Good health ; it heightens focus, increases cerebral metabolism and acts on the of. 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